Article
Engineering, Biomedical
Yixuan Lin, Yiqi Yang, Kai Yuan, Shengbing Yang, Shuhong Zhang, Hanjun Li, Tingting Tang
Summary: This study reports a three-dimensional bioprinted osteosarcoma model that incorporates osteosarcoma cells and a mimicked extracellular matrix. Compared to traditional models, this model shows significant differences in cell cycle, metabolism, and other cellular pathways, and is more sensitive to therapies targeting the autophagy pathway.
BIOACTIVE MATERIALS
(2022)
Article
Chemistry, Medicinal
Scott H. Henderson, Fiona Sorrell, James Bennett, Oleg Fedorov, Marcus T. Hanley, Paulo H. Godoi, Roberta Ruela de Sousa, Sean Robinson, Alexander Ashall-Kelly, Iva Hopkins Navratilova, Daryl S. Walter, Jonathan M. Elkins, Simon E. Ward
Summary: DYRK1A plays a crucial role in regulating the proliferation and differentiation of neuronal progenitor cells, making it a potential target for the treatment of neurodegenerative diseases and diabetes. The development of pyrazolo[1,5-b]pyridazin inhibitors with good physicochemical properties and selectivity over the kinome has opened up new possibilities for the discovery of therapies targeting DYRK1A function. Compound 11 demonstrated promising permeability and cellular activity, positioning it as a potential candidate for in vivo studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Lisa Belfiore, Behnaz Aghaei, Andrew M. K. Law, Jeremy C. Dobrowolski, Lyndon J. Raftery, Angie D. Tjandra, Christine Yee, Alberto Piloni, Alexander Volkerling, Cameron J. Ferris, Martin Engel
Summary: 3D cell models are considered more accurate in predicting the efficacy of drug responses and are seen as more physiologically representative tools for in vitro modeling of in vivo tissues. In the future, 3D cell models will continue to play an important role in drug discovery applications.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Engineering, Biomedical
Dayoon Kang, Yunji Lee, Wookyeom Kim, Hwa-Rim Lee, Sungjune Jung
Summary: We developed an all-inkjet-printed three-dimensional alveolar barrier model for anti-fibrotic drug discovery. By treating the model with pro-fibrotic cytokine, we created a fibrosis model and observed changes in structural deposition, pulmonary function, epithelial-mesenchymal transition, and fibrosis markers. Two approved anti-fibrotic drugs were tested on the model and showed alleviation of symptoms. This study highlights the potential of using bioprinting technology to create in vitro tissue models for evaluating drug efficacy.
BIOMEDICAL MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Dongwei Wu, Johanna Berg, Birte Arlt, Viola Roehrs, Munir A. Al-Zeer, Hedwig E. Deubzer, Jens Kurreck
Summary: This study developed a neuroblastoma three-dimensional model based on a human-derived environment, which can be used to test the cytotoxicity and tumor selectivity of new anticancer drugs. Compared to two-dimensional culture, this model has advantages in the width of the therapeutic window, demonstrating the value of studying anticancer drugs in human three-dimensional models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Serge Ostrovidov, Murugan Ramalingam, Hojae Bae, Gorka Orive, Toshinori Fujie, Xuetao Shi, Hirokazu Kaji
Summary: With the advances in skeletal muscle tissue engineering, new platforms have emerged for biology studies, disease modeling, and drug testing. The authors review the latest advances in in vitro models of engineered skeletal muscle tissues used for drug testing, focusing on four main cell culture techniques: well plate cultures, microfluidics, organoids, and bioprinted constructs. More developments are expected to increase the validation and use of these models in drug testing.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Baishan Jiang, Yang Gao, Jianwei Che, Wenchao Lu, Ines H. Kaltheuner, Ruben Dries, Marian Kalocsay, Matthew J. Berberich, Jie Jiang, Inchul You, Nicholas Kwiatkowski, Kristin M. Riching, Danette L. Daniels, Peter K. Sorger, Matthias Geyer, Tinghu Zhang, Nathanael S. Gray
Summary: CDK12 is a promising therapeutic target for regulating DNA damage response genes transcription, but selective small molecule development has been hindered by its homology with other transcriptional CDKs. A CDK12-specific degrader, BSJ-4-116, was successfully designed and characterized, which selectively degraded CDK12 and resulted in premature cleavage and poly(adenylation) of DDR genes.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Engineering, Biomedical
Julia Lopez de Andres, Marta Ruiz-Toranzo, Cristina Antich, Carlos Chocarro-Wrona, Elena Lopez-Ruiz, Gema Jimenez, Juan Antonio Marchal
Summary: Conventional in vitro cancer models are not able to accurately mimic the tumor microenvironment (TME). In this study, two multicellular tri-layered malignant melanoma (MM) models were bioprinted using cancer stem cells (CSCs), fibroblasts, mesenchymal stem cells, and endothelial cells. The embedded cells exhibited high proliferation, metabolic activity, and TME remodeling. The MM hydrogels displayed similar properties to skin and supported early vascularization. Furthermore, the MM hydrogels showed different response to treatment compared to cell cultures and were able to support tumorigenesis in murine xenotransplant, making them more mimetic of in vivo models.
Article
Engineering, Biomedical
Qiong Liu, Luis S. S. Mille, Cesar Villalobos, Ingrid Anaya, Matthias Vostatek, Sili Yi, Wanlu Li, Junlong Liao, Huanghui Wu, Yongteng Song, Lize Xiong, Yu Shrike Zhang
Summary: In order to effectively screen drugs, we have developed a 3D bioprinted model of cholangiocarcinoma that mimics the multicellular microenvironment and anatomical microstructure of the hepato-vascular-biliary system. By using cholangiocytes, hepatocytes, and vascular endotheliocytes for bioprinting, we were able to study the growth and drug response of cancer cells in the model. This model shows potential as a drug screening tool for cholangiocarcinoma treatment and paves the way for future personalized medicine strategies.
BIO-DESIGN AND MANUFACTURING
(2023)
Article
Biochemistry & Molecular Biology
Yixuan Lin, Kai Yuan, Yiqi Yang, Shengbing Yang, Kai Huang, Zhifeng Yu, Shuhong Zhang, Yihao Liu, Hanjun Li, Yang Dong, Tingting Tang
Summary: Recent studies have found that the relationship between osteosarcoma and matrix stiffness is often studied in a 2D environment, which may not accurately reflect the impact of matrix stiffness on cell phenotype. By using a 3D bioprinted osteosarcoma model, it was discovered that osteosarcoma cells exhibited different behaviors depending on the stiffness of the matrix. In a softer 3D matrix, the cells proliferated faster, migrated more actively, had a different morphology, and were less sensitive to drugs.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Medicinal
Csaba Weber, Melinda Sipos, Attila Paczal, Balazs Balint, Vilibald Kun, Nicolas Foloppe, Pawel Dokurno, Andrew J. Massey, David Lee Walmsley, Roderick E. Hubbard, James Murray, Karen Benwell, Thomas Edmonds, Didier Demarles, Alain Bruno, Mike Burbridge, Francisco Cruzalegui, Andras Kotschy
Summary: The kinase DYRK1A has been identified as a promising target for drug discovery, and a biaryl compound was developed through fragment screening to efficiently bind to its ATP site. Structural optimization cycles resulted in the transformation of this compound into potent and selective DYRK1A inhibitors, with a focus on fine-tuning selectivity by exploiting structural differences with DYRK2. These inhibitors demonstrated potent inhibition of DYRK1A in cell culture and in vivo, with drug-like properties and dose-dependent tumor growth inhibition in an ovarian carcinoma model.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemical Research Methods
Jianyuan Deng, Zhibo Yang, Iwao Ojima, Dimitris Samaras, Fusheng Wang
Summary: Artificial intelligence (AI) has played a crucial role in drug discovery over the past decade, with applications ranging from virtual screening to drug design. This survey provides a comprehensive overview of AI in drug discovery, covering tasks, data resources, model architectures, and learning paradigms.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Biochemical Research Methods
Yu Cheng, Yongshun Gong, Yuansheng Liu, Bosheng Song, Quan Zou
Summary: Deep generative models have gained popularity in the field of deep learning, particularly in drug discovery, showing superior performance. Researchers categorize these models into two types, analyzing their advantages and disadvantages. Although de novo molecular design automation shows promise, there are challenges to be overcome.
BRIEFINGS IN BIOINFORMATICS
(2021)
Review
Pharmacology & Pharmacy
Ke Xu, Shilin Li, Yangkai Zhou, Xinglong Gao, Jie Mei, Ying Liu
Summary: Computing has played an important role in nanodrug R&D, providing substantive solutions and making significant contributions to data-driven decision-making, reducing failure rates, and saving time costs. However, there are still issues that need to be explored and summarized to promote the high-practicability and -efficiency of computing in nanodrug discovery and development.
Review
Engineering, Biomedical
MoonSun Jung, Sarah Ghamrawi, Eric Y. Du, J. Justin Gooding, Maria Kavallaris
Summary: The tumor microenvironment is complex and difficult to replicate using traditional 2D cell culture models. The development of 3D tumor models through bioprinting technology has the potential to bridge the gap between in vitro and in vivo, offering accurate representation of the tumor microenvironment.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Oncology
Sayuri Nakamura-Bencomo, Denisse A. Gutierrez, Elisa Robles-Escajeda, Blanca Iglesias-Figueroa, Tania S. Siqueiros-Cendon, Edward A. Espinoza-Sanchez, Sigifredo Arevalo-Gallegos, Renato J. Aguilera, Quintin Rascon-Cruz, Armando Varela-Ramirez
Summary: The research shows that rhLf-h-glycan has potential toxicity against cancer cells, exhibiting selective cytotoxicity towards cancer cells while sparing normal cells. It also demonstrates significant anti-proliferative activity and induces apoptosis in cancer cells under experimental conditions.
INVESTIGATIONAL NEW DRUGS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Blanca E. Ruiz-Medina, Armando Varela-Ramirez, Robert A. Kirken, Elisa Robles-Escajeda
Summary: The origin of the COVID-19 pandemic remains unclear, with two potential scenarios being zoonotic transfer and a laboratory leak. While the Wuhan wet markets provide a strong scenario for zoonotic transfer, the lack of direct evidence remains a challenge. The laboratory origin remains plausible given the work conducted at the Wuhan Institute of Virology, highlighting the need for a definitive conclusion to prevent future pandemics.
Article
Cell Biology
Denisse A. Gutierrez, Lisett Contreras, Paulina J. Villanueva, Edgar A. Borrego, Karla Moran-Santibanez, Jessica D. Hess, Rebecca DeJesus, Manuel Larragoity, Ana P. Betancourt, Jonathon E. Mohl, Elisa Robles-Escajeda, Khodeza Begum, Sourav Roy, Robert A. Kirken, Armando Varela-Ramirez, Renato J. Aguilera
Summary: In this study, a novel pyrazole-based derivative (P3C) was found to exhibit strong cytotoxicity against various human cancer cell lines, especially triple-negative breast cancer cells. The mechanism of cytotoxicity involves the accumulation of reactive oxygen species (ROS), mitochondrial depolarization, and activation of apoptotic pathways.
Article
Oncology
Risa Mia Swain, Lisett Contreras, Armando Varela-Ramirez, Mohammad Hossain, Umashankar Das, Carlos A. Valenzuela, Manuel L. Penichet, Jonathan R. Dimmock, Renato J. Aguilera
Summary: Two novel piperidone compounds demonstrated cytotoxicity against various cancer cell lines and induced cell death through the intrinsic apoptotic pathway. They also caused cell cycle alteration and acted as proteasome inhibitors.
INVESTIGATIONAL NEW DRUGS
(2022)
Article
Chemistry, Physical
Beu P. Oropeza, Carlos Serna, Michael E. Furth, Luis H. Solis, Cesar E. Gonzalez, Valeria Altamirano, Daisy C. Alvarado, Jesus A. Castor, Jesus A. Cedeno, Dante Chaparro Vega, Octavio Cordova, Isaac G. Deaguero, Erwin Delgado, Mario F. Garcia Duarte, Mirsa Gonzalez Favela, Alba J. Leyva Marquez, Emilio S. Loera, Gisela Lopez, Fernanda Lugo, Tania G. Miramontes, Erik Munoz, Paola A. Rodriguez, Leila M. Subia, Arahim A. Zuniga Herrera, Thomas Boland
Summary: Tissue engineering utilizes bioprinting technology to address necrosis caused by nutritional deficiencies, promoting cell survival and vascularization.
Article
Biochemistry & Molecular Biology
Kwabena Owusu Dankwah, Jonathon E. Mohl, Khodeza Begum, Ming-Ying Leung
Summary: This study computationally predicted the binding of a single ligand to GPCRs from different families and uncovered similar binding pockets that contribute to ligand interactions. These findings can be applied to improve protein function inference, drug repurposing, drug toxicity prediction, and the acceleration of new drug development.
Article
Biology
Jessica D. Hess, Luca H. Macias, Denisse A. Gutierrez, Karla Moran-Santibanez, Lisett Contreras, Stephanie Medina, Paulina J. Villanueva, Robert A. Kirken, Armando Varela-Ramirez, Manuel L. Penichet, Renato J. Aguilera
Summary: This study discovered a unique thienopyrazole derivative, Tpz-1, with potent and selective cytotoxic effects on various cancer cells. Tpz-1 interferes with signaling pathways and cytoskeletal components important to cell shape, organization, growth, and division. These findings support further exploration of Tpz-1 and other thienopyrazole-based compounds as potential anticancer agents.
Article
Chemistry, Multidisciplinary
Md Nurul Huda, Isaac G. Deaguro, Edgar A. Borrego, Raj Kumar, Tamanna Islam, Humayra Afrin, Armando Varela-Ramirez, Renato J. Aguilera, Eden E. L. Tanner, Md Nurunnabi
Summary: This study developed a topical formulation composed of Navitoclax and an ionic liquid of choline octanoate. The results showed that COA-mediated topical delivery of Navitoclax was more effective in treating early-stage melanoma than oral administration.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Alice H. Grant, Alejandro C. Rodriguez, Omar J. Rodriguez J. Moncivais, Shengjie Sun, Lin Li, Jonathon E. Mohl, Ming-Ying Leung, Robert A. Kirken, Georgialina Rodriguez
Summary: Overactive Janus kinases (JAKs) are potential targets for leukemia treatment. However, a JAK1-inactivating pseudokinase mutation, V666G, was discovered instead of new JAK-activating mutations. Unlike other pseudokinase mutations, the JAK1 V666G mutation led to under-activation. It not only inhibited its own activity but also other JAK kinases. These findings provide insights into the potential modulation of JAK kinases by the JAK1 pseudokinase and the opportunity to allosterically inhibit overactive JAKs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Marine & Freshwater Biology
Rick Hochberg, Thiago Q. Araujo, Elizabeth J. Walsh, Jonathon E. Mohl, Robert L. Wallace
Summary: The retrocerebral organ (RCO) is a singular syncytial organ composed of a posterior glandular region, an expansive reservoir, and an anterior duct. The glandular portion has an active synthetic cytoplasm with paired nuclei, abundant rER, ribosomes, Golgi, and mitochondria. Granules from the gland undergo homotypic fusion to form tubular secretions that accumulate in the reservoir. The ultrastructure suggests these secretions may be hydrated glycoproteins.
INVERTEBRATE BIOLOGY
(2023)
Article
Virology
Elisa Robles-Escajeda, Jonathon E. Mohl, Lisett Contreras, Ana P. Betancourt, Bibiana M. Mancera, Robert A. Kirken, Georgialina Rodriguez
Summary: This study analyzed 3641 SARS-CoV-2 positive samples from the El Paso, Texas, community and hospitalized patients over 48 weeks from Fall 2021 to Summer 2022. The study reveals that a dominant variant, like Delta, can be rapidly replaced by a more transmissible variant, like Omicron, within a dynamic metropolitan border city, necessitating enhanced monitoring, readiness, and response from public health officials and healthcare workers.
Article
Biochemistry & Molecular Biology
Pravesh M. Jain, Denisse A. Gutierrez, Sujeet Kumar, Renato J. Aguilera, Subhas S. Karki
Summary: A series of pyrazole-oxindole conjugates were studied as potential cytotoxic agents. The compound 5-methyl-3-((3-(1-phenyl)-3-(p-tolyl)-1H-pyrazol-4-yl)methylene)indolin-2-one 6h showed the highest cytotoxic activity against Jurkat cells with a CC50 of 4.36 +/- 0.2 μM. Mechanistic studies revealed that 6h induced apoptosis in a dose-response manner, without generating reactive oxygen species (ROS) and altering mitochondrial health.
CHEMISTRY & BIODIVERSITY
(2023)
Article
Biology
Philip Lavretsky, Jonathon E. Mohl, Par Soderquist, Robert H. S. Kraus, Michael L. Schummer, Joshua I. Brown
Summary: A genomic investigation reveals that a single domestic game-farm breed of mallards is responsible for contemporary release programs in Eurasia and North America and established feral populations in New Zealand and Hawaii. Central Europe and eastern North America are identified as epicenters of ongoing hybridization, indicating that the genetic integrity of wild mallards is being affected. Self-sustaining feral populations in New Zealand and Hawaii show differentiation from their original stock and signs of local adaptation. Understanding the capacity for wildness among feral and feral admixed populations in human landscapes is crucial in the Anthropocene.
COMMUNICATIONS BIOLOGY
(2023)
Article
Materials Science, Biomaterials
Jyoti Ahlawat, Gabriela Henriquez, Armando Varela-Ramirez, Robert Fairman, Mahesh Narayan
Summary: Green-chemistry synthesized gelatin-derived carbon quantum dots (CQDs) can mitigate the neurotoxic effects of paraquat and extend organismal lifespan. The study shows that this sustainable nanomaterial can protect cell lines and organisms against neurotoxic outcomes.
BIOMATERIALS ADVANCES
(2022)